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Biomedical subjects

B Shaw

Publications and source records attributed to B Shaw.

At least 37 records · Page 2Linked to original sources

Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study.

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.

Acute Disease↗

Pilot study to evaluate the efficacy of hyperbaric oxygen therapy in improving the survival of reattached auricular composite grafts in the New Zealand White rabbit.

OBJECTIVE: This investigation is a prospective, randomized, blinded study seeking to evaluate the efficacy of hyperbaric oxygen (HBO) therapy in improving the survival of the reattached auricular composite graft. STUDY DESIGN: Twenty New Zealand White rabbits were randomly assigned to control (10) and treatment (10) groups in a prospective fashion. After amputation and reattachment of measured segments of each ear, the treatment group received 14 HBO treatments for 10 days. The control group received only standard postoperative care. On postoperative day 18, the surviving composite grafts were measured, recorded, and statistically analyzed. RESULTS: The mean percentage of graft survival for the control group was 0.31% (range 0%-2.5%), and the mean for the group receiving HBO was 15.94% (range 0%-38%). A median test was used to evaluate this difference, which was found to be statistically significant (P = 0057). CONCLUSION: Our study appears to indicate a possible survival benefit for the composite grafts in those rabbits that received HBO treatments. We believe that there are several significant difficulties with the rabbit as a model for this study, but we are encouraged at this point that a limited measurable benefit was observed. Further investigations with HBO appear to be warranted at this time.

Animals↗

Porous orbital implants and their behaviour during drilling.

The use of porous spherical orbital implants enables ocular prosthesis motility to be improved if necessary by subsequent drilling of the implant and coupling it to the prosthesis with a peg. We compared the effect of drilling at different speeds on hydroxyapatite and porous polyethylene (Medpor) spherical implants. The implants were drilled at fixed speeds of between 15 and 2000 revolutions per minute. The samples were then viewed in an electron microscope and photographed. When hydroxyapatite is drilled the porous structure of the implant is maintained although a precise hole with well-defined walls was not produced. This contrasts with porous polyethylene where the porous structure is lost although a precise drill hole is created. This drilling technique has been used successfully in patients with hydroxyapatite implants, thus making possible stable epithelialisation of the drill hole. Our results confirm that the drilling of porous polyethylene using this technique is unlikely to be successful, as loss of the porous structure would prevent stable epithelialisation of the drill hole, resulting in exposure of the implant.

Journal Article↗

The Clinical Standards Advisory Group (CSAG) Cleft Lip and Palate Study.

A national study of care and outcomes in children born with a unilateral cleft lip and palate (UCLP) was performed over a 15-month period. Two cohorts of children ('5-year-olds' and '12-year-olds') were examined. There were 57 active cleft teams in the U.K. with 105 consultant orthodontists involved in the care of these children. Only 36 teams could provide basic data such as patients names. Of the patients, 47-51 per cent had neonatal appliances. The dental arch relationships were measured with the Goslon Index and a Five-Year-Old Index, 37-39 per cent of both age groups were either 'poor' or 'very poor'. Seventy per cent of the 12-year-old patients had a Skeletal III relation and 42 per cent of bone grafts were seriously deficient or failed. Dental treatment for active caries was needed by 40 per cent of 5-year-olds and 20 per cent of 12-year-olds. In addition, the training of recently appointed consultant orthodontists involved in the care of these children was scrutinized. As a whole, the results were disappointing with standards of care not significantly raised in the last decade. Recommendations have been made to the Department of Health and the implications for the orthodontic profession are explored. Overall, it seems that fewer orthodontists will need to be involved in a centralized care model for these children.

Bone Transplantation↗

A randomized controlled trial of fluoxetine and cognitive behavioral therapy for bulimia nervosa: short-term outcome.

This study compared and combined fluoxetine and individual cognitive behavioral therapy in the treatment of bulimia nervosa. Participants were 76 women who sought treatment at the Eating Disorders Program of the Toronto Hospital and who met DSM-III-R criteria for bulimia nervosa. Subjects were randomly assigned to receive fluoxetine alone, cognitive behavior therapy alone, or the two in combination and were treated over 16 weeks. Short-term outcome revealed that all three treatment conditions were associated with clinical improvement across a wide range of parameters. The combination of pharmacotherapy and psychotherapy was superior to pharmacotherapy alone on specific parameters and there was no statistically significant advantage to the combination over psychotherapy alone. Limitations to the study include the absence of a placebo pill group and a waiting list control group as well as a substantial dropout rate across all three treatment conditions.

Adolescent↗

Randomised trial of effect of delayed intravenous lipid administration on chronic lung disease in preterm neonates.

A recent sevenfold increase in the annual incidence of chronic neonatal lung disease (CNLD) on an intensive care unit was attributed to the early administration of intravenous lipid (IVL) in ventilated preterm neonates. When logistic regression was used to eliminate other confounding variables, early delivery of IVL was independently associated with an eight-fold increase in the likelihood of CNLD. Consequently, we designed a prospective study to detect a halving of the incidence of CNLD by delaying IVL administration from 5 days (as is routine practice) to 14 days. Sixty-four parenterally fed preterm neonates weighing < 1,500 g at birth were randomised to receive IVL either on day 5 or day 14. Analysis was by intention to treat, since several infants in the latter group required no parenteral nutrition by day 14. Our results showed that the relative risk (95% confidence interval) of CNLD at 28 postnatal days was 1.15 (0.81-1.62); at 36 weeks postconception, it was 1.08 (0.59-1.99). A study population of > 2,000 would be required to determine whether these relative risks were significantly different from 1.

Chronic Disease↗

Analysis of charges associated with diagnosis of nosocomial pneumonia: can routine bronchoscopy be justified?

Many ventilated trauma patients thought to have nosocomial pneumonia have pulmonary contusion or systemic inflammatory response syndrome with tracheobronchial colonization. Fiberoptic bronchoscopy with quantitative culture techniques of protected specimen brush (PSB; threshold 10(3) cfu/mL) or bronchoalveolar lavage (BAL; threshold 10(5) cfu/mL) can potentially eliminate the false positive cultures of the upper airway seen with routine sputum aspirates (RS). However, bronchoscopy is expensive, and routine use may not be cost effective. This prospective study evaluated the patient charges associated with bronchoscopy and quantitative cultures compared with RS for the diagnosis of nosocomial pneumonia. Specimens were obtained by RS, PSB, and BAL from the lower airway in 107 trauma patients (136 sets of triplicate cultures). All patients had clinical evidence suggestive of pneumonia (fever, leukocytosis, purulent sputum, abnormal roentgenographic findings). Typical oral flora were considered contaminants; no gram-negative specimens were excluded. Mean age was 40 years and mean ISS was 29. Seventy-eight percent had blunt injuries, 22% penetrating, and 42% had chest injuries. The incidence of nosocomial pneumonia according to each method was: RS-73%; PSB-34%; BAL-25%. Considering all charges involved (bronchoscopy, equipment, microbiologic analysis, and antibiotics), and based on a 14-day course of ceftazidime and vancomycin, the charges for PSB were 58% of RS, and charges for BAL were 43% of RS. We conclude that the charges associated with bronchoscopy are high, but can be offset by antibiotic savings. Side effects of unnecessary antibiotic therapy would be avoided. Further study is needed to determine the efficacy of PSB or BAL in trauma patients.

Adult↗

Reinfusion of shed blood after orthopaedic procedures in children and adolescents.

A prospective study was done of the results of infusion of drained blood after major procedures on the spine and hip in twenty-six patients. The Solcotrans system was used to salvage drained blood in the first six hours after the operation. Transfusion requirements, blood loss, hematocrit, temperature, prothrombin time, partial prothrombin time, platelet count, results of blood cultures, and levels of factor VIII, factor V,D-dimer, antithrombin III, plasminogen, protein C, and complement C3a des arginine were determined for some or all of the patients. A mean of 375 milliliters of blood from the Solcotrans receptacle was reinfused. All of the cultures were negative. There were no febrile reactions. The mean values for the specimens of the salvaged blood were: hematocrit, 0.20; hemoglobin, seventy-one grams per liter; plasma hemoglobin, 2.36 grams per liter; C3a des arginine, 9.4 x 10(-3) grams per liter; fat particles of less than nine micrometers in diameter, 23,643 per milliliter; and D-dimer, 205 x 10(-3) grams per liter. Studies of blood samples that were collected from patients one to two hours and twelve to eighteen hours after the transfusion showed only slight increases in fibrin split products one hour after the transfusion; these values reverted to normal by eighteen hours. No clinical coagulopathy associated with reinfusion was observed. The reinfusion of unwashed, filtered shed blood that was as much as 15 per cent of the total blood volume proved to be a safe technique after major orthopaedic procedures.

Adolescent↗

A multicentre comparison of treatment regimens for unilateral cleft lip and palate using a multiple regression model.

The European Cleft Lip and Palate Research Group consists of specialists in orthodontics from six centres for the treatment of cleft palate in northern Europe. The purpose of this part of the multicentre study was to investigate whether differences in outcomes could be explained by specific treatment regimens. Three regimens that were assumed to influence the outcome of treatment were selected: Presurgical orthopaedics, closure of the palate, and primary bone grafting. The sample comprised 151 children with complete unilateral cleft lip and palate from the six centres. The result of multiple regression analysis showed that within that sample it was not possible to reach definite conclusions as to which factors exerted the most favourable influence on facial growth, but primary bone grafting was associated with reduced maxillary inclination and presurgical orthopedics with increased mandibular inclination.

Bone Transplantation↗

Inhibition of preimplantation mouse embryo development by isoflurane.

OBJECTIVE: Preimplantation mouse embryos were exposed to a commonly used inhalational anesthetic agent, isoflurane, to determine its effects on embryo development. STUDY DESIGN: Two-cell embryos were exposed at various intervals (5 to 6 hours, 3 to 4 hours, and 0 to 1 hour) before the onset of their first cleavage in vitro. In addition, the effects of 5% isoflurane on four-cell embryos exposed about 2 hours after the first cleavage and morula stage embryos also were examined. RESULTS: Development to the blastocyst stage was inhibited by 3% and 5% isoflurane (p less than 0.005) but not by 1.5% isoflurane when two-cell embryos were exposed 3 to 4 hours or 0 to 1 hour before the onset of cleavage. Most of the affected embryos completed cell division and came to a halt at the three- to four-cell stage. The development of embryos exposed to isoflurane at the four-cell or morula stage was unaffected. CONCLUSIONS: Isoflurane adversely affects subsequent preimplantation development when two-cell mouse embryos are exposed just before the onset of their first cleavage in vitro.

Animals↗

MK-507 versus sezolamide. Comparative efficacy of two topically active carbonic anhydrase inhibitors.

Topical carbonic anhydrase inhibitors MK-507 and sezolamide hydrochloride (previously known as MK-417) were compared in a double-masked, randomized, placebo-controlled study in 82 patients with bilateral primary open-angle glaucoma or ocular hypertension. MK-507 was given every 8 or 12 hours, sezolamide every 8 hours, or placebo every 8 or 12 hours for 4 days. Both drugs lowered intraocular pressure (IOP) substantially. MK-507 was somewhat more active than sezolamide, with a peak mean IOP reduction of 26.2% for MK-507 versus 22.5% for sezolamide, although the difference between the treatments was not statistically significant. These drugs may have potential in the treatment of glaucoma.

Administration, Topical↗

New developments in the drug treatment of glaucoma.

This article reviews standard treatment modalities for patients with glaucoma and describes 3 classes of drugs which are undergoing development: apraclonidine (aplonidine, ALO 2145), an alpha 2-adrenergic agonist which has been released for clinical use; topical carbonic anhydrase inhibitors, a modification of the systemic carbonic anhydrase inhibitors currently in use; and prostaglandins (PGs), a new class of drugs with topical ocular hypotensive activity. Standard treatment modalities include parasympathomimetic agents such as pilocarpine, carbachol, and phospholine iodide, which lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork. A newer form of pilocarpine as a gel produces a longer action. Adrenergic agonist medications, such as epinephrine (adrenaline) and its prodrug dipivefrine (dipivalyl epinephrine), function by increasing uveoscleral outflow and trabecular outflow facility. A decrease in aqueous formation by the ciliary processes is thought to be the mechanism of action of beta-adrenoceptor antagonists, but the physiological basis for this action has not been clearly demonstrated. A newer beta-blocker, betaxolol, has relatively selective beta 1-blocking activity. Carbonic anhydrase inhibitors are nonbacteriostatic sulphonamide derivatives which decrease aqueous formation by the ciliary body. Almost 50% of patients taking these medications are unable to tolerate them because of their adverse effects, and there is thus much interest in the development of a topical carbonic anhydrase inhibitor with the potential for fewer adverse effects. MK 507 is the most recent and most potent compound in the series of topically active carbonic anhydrase inhibitors. Apraclonidine hydrochloride is a derivative of clonidine hydrochloride, an alpha 2-adrenergic agonist. Clonidine has previously been shown to lower IOP significantly, but has the potential to produce marked lowering of both systolic and diastolic blood pressures. Its major ocular effect appears to be a decrease in aqueous production. The structural modification to apraclonidine decreases corneal absorption and the drug's ability to cross the blood-brain barrier, minimising the risk of centrally mediated cardiovascular side effects. Apraclonidine may also influence secondary avenues of aqueous outflow, such as uveoscleral outflow, and may also affect conjunctival and episcleral vascular flow. It produces a mean decrease in IOP of 25% for as long as 12 hours. Adverse effects include blanching of the conjunctiva, minimal mydriasis and eyelid retraction. This drug has been approved in the US for use in prevention of elevated IOP after argon laser trabeculoplasty and iridotomy, and has potential uses in preventing an IOP rise after YAG laser posterior capsulotomy and cataract surgery in patients already on other antiglaucomatous medications.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗

Histopathologic validation of Fourier-ellipsometry measurements of retinal nerve fiber layer thickness.

We describe a new technique for the measurement of retinal nerve fiber layer thickness and compare its results with histopathologic measurements in the same eyes. For these studies, two fixed monkey eyes were incised and placed on a pedestal in a plastic viewing dish. The eyes were perfused to maintain a pressure between 10 and 20 mm Hg. An ellipsometer, an optical device used to measure the change in polarization of light (retardation), was implemented in a laser tomographic scanner to obtain polarization data from the two monkey retinas. For the 15 measured locations, retardation ranged between a mean (+/- SD) of 0.9 degrees +/- 1.8 degrees and 23.7 degrees +/- 0.3 degrees. Subsequently, retinal nerve fiber layer thickness was measured at the imaged points in epoxy resin-embedded sections by an observer masked to the ellipsometry data. These values ranged between 20.4 microns and 213.9 microns. There was an excellent correlation (R = .83) between retardation and the histopathologic measurement of retinal nerve fiber layer thickness. Quantitating retinal nerve fiber layer thickness may enhance discrimination between glaucomatous and normal eyes earlier than is currently available by anatomic and functional approaches.

Animals↗